| 초록 |
The renin-angiotensin system (RAS) plays a critical role in the regulation of
blood pressure and body fluid homeostasis. In addition to its physiological roles,
angiotensin II (AngII) induces inflammation, cell growth, mitogenesis, apoptosis,
migration, and differentiation, regulates the gene expression of bioactive
substances, and activates multiple intracellular signaling pathways, all of which
contribute to renal tissue injuries. In the kidney, all of the RAS components are
present and intrarenal AngII is formed by independent multiple mechanisms. In
particular, a series of our studies have revealed that intrarenal angiotensinogen
plays a predominant role in the regulation of AngII production in the kidney.
Consequently, AngII is compartmentalized in the renal interstitial fluid and the
proximal tubular compartments with much higher concentrations than those
existing in the circulation. Recent evidence has also revealed that inappropriate
activation of the intrarenal RAS is an important contributor to the pathogenesis of
hypertension and renal injury. For example, circulating plasma AngII levels are
reduced in CKD patients with salt-dependent hypertension; however, intrarenal
RAS is activated by inappropriately augmentation of angiotensinogen in the
kidney. Thus, it is necessary to understand the mechanisms responsible for
independent regulation of the intrarenal RAS. In this symposium, I will briefly
summarize our current understanding of independent regulation of the intrarenal
RAS and discuss how inappropriate activation of this system contributes to the
development of salt-dependent hypertension on patients with CKD. We will also
discuss the possible biomarker of the intrarenal RAS. |